This laboratory has used measurements of desmosine and isodesmosine as an accurate indication of the presence of elastin or elastin degradation products. We recently developed a radioimmunoassay for desmosines, which has increased the sensitivity of our measurements by approximately 500-fold. With this technique, we believe it will be possible to study the metabolic turnover of insoluble elastin in normal and disease conditions from man and experimental animals. We previously demonstrated the presence of elastase in the alveolar macrophages of cigarette smokers. Efforts during the coming year will include the establishment of roller bottle cultures so that large numbers of macrophages can be obtained. We plan to study the composition and physiological characteristics of this elastase. We have recently shown that the fibroblasts obtained from the fetal calf neck ligament is capable of synthesizing soluble elastin precursors in confluent cultures. We plan to develop a radioimmunoassay to elastin (a high titer elastin antibody is already available) and study the factors which influence elastin synthesis. The technique should permit us ultimately to demonstrate the cell sites of elastin synthesis in tissues. Finally, we plan to study the synthesis of elastin by fibroblasts under continuous mechanical stimulation of cyclic strain. The cells will be grown on a membrane subjected to cyclic tension sufficient to produce a physical elongation of the membrane. There is good influential histologic evidence to suggest that such mechanical factors may be important for the synthesis and deposition of insoluble elastin.